Lymphatic Mapping and Sentinel Node Biopsy in Vulvar, Vaginal, and Cervical Cancers

ABSTRACT: ABSTRACT: Over the past 15 years, lymphatic mapping and sentinel lymph node biopsy in vulvar, vaginal, and cervical cancers have been explored by gynecologic oncologists around the world. Based on the results of multiple single-institution studies, most in our field are optimistic that these techniques will increase the rates of detection of lymph node metastasis while decreasing the morbidity associated with lymphadenectomy. Large validation studies are currently underway in both the United States and Europe. In this review article, we present the published data on mapping techniques and discuss future considerations for these technologies.

In 1977, Cabanas reported his initial experience with lymphatic mapping and sentinel lymph node detection in men with penile cancer.[1] He hypothesized that tumors spread from the primary lesion to the draining nodal basins in an orderly, predictable pattern and that tumor emboli would not "skip" primary draining nodal basins for upper-echelon nodes. These initial draining basins were termed "sentinel nodes," as they were metaphorically the lookouts for all upper-echelon, or nonsentinel, nodes. A more modern and succinct definition of a sentinel lymph node is "any lymph node that receives lymphatic draining directly from a tumor site."[2]

Although the early pioneering studies in lymphatic mapping and sentinel lymph node biopsy were in patients with penile cancer, it was breast and melanoma surgeons who led the majority of the research in the 1980s and 1990s.[3,4] Currently, lymphatic mapping and sentinel lymph node biopsy, in lieu of complete regional lymphadenectomy, are the standard of care for breast cancers and melanomas. This technique has also been explored in other malignancies, including cancers of the head and neck, oropharynx, thyroid, stomach, colon, and bladder. In the past 15 years, lymphatic mapping has been explored in almost all of the gynecologic malignancies, including those of the vulva, vagina, cervix, and uterus.

A variety of technologies exist to help surgeons locate the sentinel nodes. Preoperative lymphoscintigraphy uses a radiolabeled colloid injected peritumorally to identify the sentinel node. A scanning machine detects the gamma emissions from the colloid (typically technetium-99) after it has drained to the sentinel lymph node. Gamma emissions from a radiolabeled colloid can also be followed intraoperatively using a handheld gamma probe to pinpoint the sentinel node. Patent blue dyes may also be injected peritumorally for visual identification of sentinel nodes during surgery. Resected sentinel nodes may therefore be "hot" (positive for the radiolabeled colloid), "blue" (positive for patent blue dye), or both hot and blue. Most studies of lymphatic mapping for breast cancer and melanoma have found that a combination of radiolabeled colloid and blue dye leads to higher sentinel node detection rates. This appears to hold true for the gynecologic malignancies, as will be discussed in this review.

The objective of this article is to review the current literature on lymphatic mapping and sentinel node detection in women with gynecologic malignancies. We will pay particular attention to the rationale for mapping, the reliability of the techniques, the localization of sentinel nodes, and the utility of pretherapeutic lymphoscintigraphy. Among studies of cervical and vulvar cancers, there are multiple case reports, small series (< 20 patients), and large series (≥ 20 patients). We included only those series with more than 20 patients in our review, since a long-recognized limitation of lymphatic mapping is the higher rate of false-negative sentinel node detection in the first few cases a surgeon performs.[5,6] By restricting the eligible studies in this manner, we hoped to assure that the individual surgeons in each reported series would have obtained proficiency (ie, master the "learning curve") in sentinel lymph node mapping for gynecologic malignancies.

Vulvar Cancer

Epidemiology

An estimated 3,490 new cases of vulvar cancer were diagnosed in the United States in 2007, and an estimated 880 deaths resulted from the disease.[7] Most vulvar cancers have squamous cell histologies (more than 90%), with melanoma accounting for the majority of the remaining tumors.

For patients with clinical stage I squamous cell carcinoma of the vulva, the risk of lymph node metastasis is 10.7%. This risk increases to 26.2% for clinical stage II disease and to 64.2% for clinical stage III disease.[8] The lymphatic drainage of the vulva is almost exclusively to the inguinofemoral triangle, which could be considered a sentinel lymph node basin. Although some anatomists have hypothesized that lymph drains directly from the vulva to the pelvis, this route has never been demonstrated clinically. Unilateral vulvar lesions, typically defined as tumors located more than 2 cm from the midline, primarily drain primarily to the ipsilateral groin nodes.

Unilateral and bilateral inguinofemoral lymphadenectomies have relatively high rates of postoperative complications, with as many as two-thirds of patients experiencing wound breakdown, lymphocyst formation, and/or lymphedema as a result of their groin dissection.[9] For this reason, and because vulvar cancers have a highly predictable anatomic drainage pattern, lymphatic mapping and sentinel node dissection are seemingly ideal for this disease site.

Success of Lymphatic Mapping

TABLE 1

Summary of Published Literature on Lymphatic Mapping in Patients With Vulvar Cancer

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